Tibor Kovacsovics

Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial

Background Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old. Design and Methods We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine. Results The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49–1.35) for survival and of 0.67 (95% CI, 0.42–1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22–1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22–1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40–3.42) and that for disease-free survival was 1.02 (99% CI, 0.40–2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65–2.27) for survival and 1.02 (95% CI, 0.56–1.85) for disease-free survival. Conclusions Patients with a donor and candidates for allogeneic stem cell transplantation in first complete remission may have a better disease-free survival than those without a donor in case of myelodysplastic syndromes with intermediate/high-risk cytogenetics. Autologous peripheral blood stem cell transplantation does not provide longer survival than intensive chemotherapy. (Eudract number: NCT00002926; http://www.cancer.gov/clinicaltrials/EORTC-06961)

Recurrent cytomegalovirus disease, visceral leishmaniosis, and Legionella pneumonia after liver transplantation: a case report

PurposeRecurrent cytomegalovirus (CMV) disease is a frequent complication of liver transplantation. Visceral leishmaniosis in a transplant recipient is, on the other hand, extremely rare and only two cases of kala-azar have been described after liver transplantation. Immunosuppressed patients are known to be at risk of Legionella infection and the relationship between infection with this organism and hospital water supplies has been well described. These three diseases carry a high mortality rate. Our report examines the potential relationship between these complications.Clinical featuresWe describe the case of a liver transplant recipient who presented the three complications successively and survived. After reviewing the literature, we explore hypotheses linking these infections and discuss treatment strategies.ConclusionsIn the patient described, infection with leishmania probably occurred months prior to the clinical presentation, a delay that matches the incubation period of kala-azar. The simultaneous onset of leishmaniosis and of a high CMV viremia may have been a coincidence. However, CMV infection has been shown to be an independent predictor of invasive fungal infection in liver transplant recipients. CMV does indeed have a suppressive effect on the humoral and cellular immune responsein vitro as well asin vivo. The clinical manifestations of leishmaniosis may, therefore, have been precipitated in this patient by the additive immunosuppressive effect of antirejection drugs and CMV.RésuméObjectifL’linfection récurrente au cytomégalovirus (CMV) est une complication fréquente de la transplantation hépatique. La leishmaniose viscérale chez un receveur d’organe est, par contre, extrêmement rare et on ne rapporte que deux cas de kalaazar à la suite d’une greffe de foie. Les patients immunodéprimés sont à risque d’infections à Légionella et la relation entre cet organisme et l’alimentation en eau des hôpitaux a été bien décrite. Ces trois maladies présentent un taux de mortalité élevée. Nous étudions ici la relation possible entre ces complications.Éléments cliniquesNous décrivons le cas d’un patient greffé du foie qui a présenté successivement les trois complications et a survécu. Après avoir passé en revue les publications, nous explorons des hypothèses pouvant relier ces infections et discutons des traitements possibles.ConclusionChez ce patient, l’infection à Leishmania est probablement survenue plusieurs mois avant les manifestations cliniques, ce qui correspond à la période d’incubation du kalaazar. La survenue simultanée d’une leishmaniose et d’une importante virémie au CMV pourrait n’être qu’une coïncidence. Cependant, l’infection au CMV s’est révélée un prédicteur indépendant d’infection fongique invasive chez les receveurs d’un foie. Le CMV a certainement un effet inhibiteur sur la réponse immunitaire humorale et cellulaire, in vitro aussi bien qu’in vivo. Les manifestations cliniques de la leishmaniose peuvent donc avoir été précipitées par l’effet immunodépresseur supplémentaire des médicaments antirejet et du CMV.

Peritoneal Tuberculosis After Imatinib Therapy

I matinib mesylate, a selective inhibitor of the BCRABL tyrosine kinase gene, is now a standard therapy in patients with chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). Recent studies have shown that imatinib alters T-cell–mediated immune responses, raising the possibility of opportunistic infections associated with imatinib therapy. So far, few epidemiological data are available to support this hypothesis. We report herein a case of peritoneal tuberculosis (TB) following 4 months of imatinib therapy for CML.

A rapid and efficient method for the purification of the complement subcomponents C1r and C1s in zymogen form using fast protein chromatography

The purification of the subcomponents C1r and C1s of the first component of complement involves multiple steps and is time-consuming. This accounts for the frequently observed partial activation of the subcomponents. In this report we propose a simplified procedure of purification using a batch method and fast protein chromatography avoiding a shift of pH. The method provides C1r and C1s in a yield of 35 and 60% respectively. In addition, this study provides a simple and sensitive test to assess functional purity of C1r and C1s with respect to the other C1 subcomponents.